Visible-light induced dearomatization reactions

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(6), P. 2145 - 2170

Published: Jan. 1, 2022

This review provides an overview of visible-light induced dearomatization reactions classified based on the manner in which aromaticity is disrupted.

Language: Английский

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Energy-Transfer-Enabled Dearomative Cycloaddition Reactions of Indoles/Pyrroles via Excited-State Aromatics

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(17), P. 2510 - 2525

Published: Aug. 9, 2022

Exploring the enormous chemical space through an expedient building-up of molecular diversity is important goal organic chemistry. The development synthetic methods toward molecules with unprecedented structural motifs lays foundation for wide applications ranging from pharmaceutical chemistry to materials science. In this regard, dearomatization arenes has been recognized as a unique strategy since it provides novel retrosynthetic disconnections various spiro or fused polycyclic increased saturation and stereoisomerism. However, inherent thermodynamic challenges are associated processes. disruption aromaticity arene substrates usually requires large energy inputs, which makes harsh conditions necessary many ground-state reactions. Therefore, further expansion scope reactions remains major problem not fully solved in chemistry.The past decade witnessed tremendous progress on photocatalytic under visible light. Particularly, via transfer mechanism have unlocked new opportunities Mediated by appropriately chosen photosensitizers, aromatic can be excited. This kind precise input might make feasible some that otherwise unfavorable thermal because significant increases substrates. Nevertheless, lifetimes key intermediates energy-transfer-enabled reactions, such excited-state aromatics downstream biradical species, quite short. How regulate reactivities these transient achieve exclusive selectivity certain reaction pathway among possibilities crucial issue addressed.Since 2019, our group reported series visible-light-induced dearomative cycloaddition indole pyrrole derivatives. It was found units excited irradiation light presence suitable photosensitizer. These readily undergo [m + n] tethered unsaturated functionalities including alkenes, alkynes, N-alkoxy oximes, (hetero)arenes, vinylcyclopropanes. yield indolines pyrrolines highly strained small- and/or medium-sized rings embedded, possess bridge- cagelike topologies. Systematic mechanistic studies confirmed involvement process. Density functional theory (DFT) calculations revealed correlation between substrate structure excitation efficiency, accelerated optimization parameters. Meanwhile, DFT demonstrated competition kinetically thermodynamically controlled pathways open-shell singlet intermediates, allowed complete switches [2 2] 1,5-hydrogen atom oximes [4 naphthalene. Furthermore, ab initio dynamics (AIMD) simulations uncovered post-spin crossing dynamic effects, determine regioselectivity recombination step pyrrole-derived vinylcyclopropanes.An increasing number scientists joined research contributed more elegant examples area. mechanism, although still its infancy, exhibited great potential synthesis hardly accessed other methods. We believe future will push boundary find related disciplines.

Language: Английский

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Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(33), P. 13441 - 13449

Published: Aug. 16, 2021

Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, by excitation aromatic rings provide an alternative solution to direct transformations feedstocks under scheme dearomatization. Vinylcyclopropanes (VCPs) well-known reagents in radical clock experiments, working a probe detect transient intermediates. However, applications this regard still remain limited due uncontrollable selectivities. Herein, we report visible-light-induced dearomatization indole- or pyrrole-tethered VCPs, which several competitive reaction pathways, including [5 + 2], [2 interrupted and 4] cycloadditions, can be well regulated engineering substrate structures tuning conditions. The mechanism has been explored combined experimental computational investigations. These convenient method synthesize structurally diverse polycyclic with high efficiency good selectivity.

Language: Английский

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Visible‐Light‐Induced Intramolecular Double Dearomative Cycloaddition of Arenes

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(13), P. 7036 - 7040

Published: Jan. 15, 2021

Abstract Herein we report visible‐light‐induced intramolecular double dearomative cycloaddition of arenes. Compared with the well‐known photodimerization arenes under ultraviolet irradiation, current reactions are carried out mild conditions and feature wide substrate scope. A large array structurally‐diverse polycyclic indoline derivatives is afforded in high yields (up to 98 %) exclusive diastereoselectivity (>20:1 dr) via [4+2] or [2+2] pathway.

Language: Английский

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Photochemical Dearomative Cycloadditions of Quinolines and Alkenes: Scope and Mechanism Studies

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(38), P. 17680 - 17691

Published: Sept. 15, 2022

Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para-cycloadditions are rare. Herein, method achieve photochemical of quinolines alkenes is shown. Emphasis placed on generating sterically congested products reaction highly substituted allenes. In addition, the mechanistic details process studied, which revealed reversible radical addition selectivity-determining recombination. The regio- stereochemical outcome also rationalized.

Language: Английский

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Facile access to fused 2D/3D rings via intermolecular cascade dearomative [2 + 2] cycloaddition/rearrangement reactions of quinolines with alkenes

Nature Catalysis, Journal Year: 2022, Volume and Issue: 5(5), P. 405 - 413

Published: May 25, 2022

Abstract Hybrid fused two-dimensional/three-dimensional (2D/3D) rings are important pharmacophores in drugs owing to their unique structural and physicochemical properties. Preparation of these strained ring systems often requires elaborate synthetic effort exhibits low efficiency, thus representing a limiting factor drug discovery. Here, we report two types energy-transfer-mediated cascade dearomative [2 + 2] cycloaddition/rearrangement reactions quinoline derivatives with alkenes, which provide straightforward avenue 2D/3D pyridine-fused 6−5−4−3- 6−4−6-membered systems. Notably, this strategy features excellent diastereoselectivity that bypasses the general reactivity selectivity issues photochemical cycloaddition various other aromatics. Tuning aza-arene substitutions enabled selective diversion iridium photocatalysed energy transfer manifold towards either cyclopropanation or cyclobutane-rearrangement products. Density functional theory calculations revealed scenario be operative.

Language: Английский

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Photochemical dearomative skeletal modifications of heteroaromatics

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(12), P. 6600 - 6624

Published: Jan. 1, 2024

Dearomatization has emerged as a powerful tool for rapid construction of 3D molecular architectures from simple, abundant, and planar (hetero)arenes. The field evolved beyond simple dearomatization driven by new synthetic technology development. With the renaissance photocatalysis expansion activation mode, last few years have witnessed impressive developments in innovative photochemical methodologies, enabling skeletal modifications dearomatized structures. They offer truly efficient useful tools facile highly complex structures, which are viable natural product synthesis drug discovery. In this review, we aim to provide mechanistically insightful overview on these innovations based degree alteration, categorized into dearomative functionalization editing, highlight their utilities.

Language: Английский

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Synthesis of complex bicyclic scaffolds by intermolecular photosensitized dearomative cycloadditions of activated alkenes and naphthalenes

Chemical Science, Journal Year: 2022, Volume and Issue: 13(45), P. 13582 - 13587

Published: Jan. 1, 2022

The rapid buildup of molecular complexity from simple precursors is a key goal in organic chemistry. One strategy to achieve this through dearomative cycloaddition wherein 2D arene and alkene converted 3D structure. In many cases type reactivity has been achieved with photochemistry. Despite the prospect such reaction, most known variants are intramolecular, which greatly limits scope chemical space that can be accessed. Intermolecular but generally limited heterocyclic systems as indoles or quinolines. Herein, method for intermolecular naphthalenes alkenes presented. reactions operate by photoinduced sensitization arene. bridged bicyclic products generated control regiochemistry function range alkenes. addition, serve useful intermediates demonstrated synthesis biologically active benzazapine analog. Mechanistic studies also included, support reaction via triplet excited state selectivity rationalized spin-density calculations.

Language: Английский

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Dearomatization of (Hetero)arenes through Photodriven Interplay between Polysulfide Anions and Formate**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 16, 2023

Abstract The facile construction of C(sp 3 )‐rich carbo‐ and heterocyclic compounds is a pivotal synthetic strategy to foster contemporary drug discovery programs. downstream dearomatization readily accessible two‐dimensional (2D) planar arenes represents direct pathway towards accessing three‐dimensional (3D) aliphatic scaffolds. Here, we demonstrate that polysulfide anions are capable catalyzing process substituted naphthalenes, indoles, other related heteroaromatic in the presence potassium formate methanol under visible light irradiation. developed protocol exhibits broad functional group tolerance, operational simplicity, scalability, cost‐effectiveness, representing practical sustainable tool for arene dearomatization.

Language: Английский

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Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(48)

Published: Oct. 7, 2023

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation Birch are two broadly utilized approaches (hetero)arene across academia industry over last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline isoquinoline protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom (HAT). The design this bypasses conventional metric reaction, that is, reductive potential, instead relies on triplet energies chemical moieties kinetic barriers events. Many reducing labile functional groups, were incompatible with previous reactions, retained in reaction. anticipate will trigger further advancement arene enable current arene-rich drug space to escape from flatland.

Language: Английский

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